Autophagy is a cellular catabolic process through which cytoplasmic materials are targeted for lysosomal degradation via a series of intracellular vesicular formation and fusion events. After lysosomal degradation, biological bulding blocks and energy can be recycled to maintain essential cellular activity. Autophagy is required for various biological processes and is closely associated with a number of human diseases including cancer. The long-term goal of this proposal is to understand the molecular basis of autophagy in mammalian cells and to dissect the role of autophagy in cancer. Specifically, in this proposal I will (1) determine the molecular mechanisms by which LRRFIP1, a novel autophagic protein I recently identified, regulates autophagy;and (2) investigate the role of autophagy in cancer development and treatment by using an RCAS-tva based mouse model for glioblastoma. To achieve these goals, a combination of biochemical, cellular and molecular biological, and animal modelling techniques will be used. Success of this study will not only lead to the understanding of novel molecular mechanisms underlying mammalian autophagy, but will also provide insights into development of novel cancer therapeutic approaches that target autophagy. PUBLIC HEALTH RELEVANCE: Success of this study will not only lead to the understanding of novel molecular mechanisms underlying mammalian autophagy, but will also provide insights into development of novel cancer therapeutic approaches that target autophagy.